This study aimed to investigate whether NKAP (nuclear factor κB activating protein) serves as a prognostic marker and predictive biomarker for immunotherapy response in head and neck squamous cell carcinoma (HNSCC).

A retrospective cohort study combined with in vitro analyses was conducted. NKAP mRNA expression levels were assessed in 520 HNSCC tumor tissues and 44 normal tissues from the TCGA dataset and validated in a clinical cohort (n = 32). Clinical correlations with overall survival and immunotherapy outcomes were analyzed. The key pathological variables included tumor stage, grade, HPV status, and TP53 mutation. Appropriate statistics were calculated at a significant level (P < 0.05).

In this study, we have collected tissue samples from HNSCC patients (mean age: 52.65 ± 7.76; males 66%, females 34%). NKAP was upregulated in HNSCC tissues compared to adjacent normal tissues (P < 0.001). The high expression of NKAP correlated with advanced tumor stage, grade, and reduced survival (P < 0.05). High expression levels of NKAP were also associated with anti-PD-L1 therapy response (P < 0.05). Functional enrichment analysis revealed NKAP involvement in cell cycle regulation, mRNA processing, and chromatin remodeling pathways critical for cancer progression.

NKAP represents a promising prognostic marker and therapeutic target for immunotherapy in HNSCC. Prospective studies are warranted to confirm these findings.